P677: THE FACTORS OF LATE MOLECULAR RELAPSES AFTER TYROSINE KINASE INHIBITORS DISCONTINUATION IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Authors: Anna Petrova, Oleg Shukhov, Ekaterina Chelysheva, Margarita Gurianova, Irina Nemchenko, Anastasia Bykova, Elena Kuzmina, Anna Turkina
Journal: HemaSphere (2023)

Background: The frequency of late molecular relapses (LMR) in patients (pts) with chronic myeloid leukemia (CML) after tyrosine kinase inhibitors (TKIs) treatment discontinuation is 10-12% according to the literature (Richter et al, 2020), which determines lifelong molecular control in these pts. The treatment duration was significant factor for the development of early molecular relapses. The search for simple and practical predictors of LMR is an important goal for a wider implementation of observation in treatment-free remission (TFR) in clinical practice. Aims: To analyze the prognostic factors for LMR after TKIs discontinuation in CML pts in RU-SKI study. Methods: Ninety eight CML patients with TKI therapy duration ≥ 3 years and deep molecular response (DMR, BCR::ABL1≤ 0.01% IS) duration ≥ 2 years were included in prospective study RU-SKI. Molecular relapse and TKIs restart was in a case of major MR (MMR, BCR::ABL1>0,1%) loss, evaluated by real-time polymerase chain reaction. We considered the loss of MMR more than 6 months (mo) after treatment discontinuation as LMR and used 6-months landmark for LMR analysis. We used the Kaplan-Meier method, the cumulative incidence function (CIF) with the log-rank test for comparison and the Gray test for multiple comparisons. Differences were considered statistically significant at p ≤ 0.05. Results: The characteristics of the patients are presented in table 1. Median (Me) time of follow-up without therapy was 55 mo (8-78 mo). Fifty six (57%) out of 98 pts remained in TFR during first 6 mo after treatment discontinuation and were included in analysis. Subsequent loss of MMR was in 8 (14%) pts within a period of 8 to 47 mo (Ме time of MMR loss = 16 mo) after TKI discontinuation. Survival without MMR loss was 92% (CI 86-99%), 89% (CI 81-97%) and 84% (CI 73-94%) at 12, 36 and 60 mo after 6-months landmark respectively (figure 1). We have found no differences in LMR probability depending on the previous duration of TKI therapy. Also no differences (p=0,317) in LMR probability was observed in pts groups with undetectable BCR::ABL1 (n=23, MR5) and detectable BCR::ABL1 level (n=33) during the first 6 mo after TKI stop. Next, we assessed the probability of LMR depending on the maximum BCR::ABL1 level during the 6 mo after treatment discontinuation: MR3 (loss of MR4), MR4, MR4.5 or MR5 (see table1). We united pts with MR4, MR4.5, MR5 into 1 group (MR≥4, n=44) and compared with the pts group with MO4 loss (n=12). We confirmed the association between MR4 loss during the first 6 months and LMR development: the probability of LMR was 50% in the pts with MR3 versus 7% in pts with MR≥4 (p<0.0001, figure 2). Summary/Conclusion: Only 14% patients, who maintained TFR during the first 6 months after treatment discontinuation, experienced LMR. Loss of MR4 in the first 6 months after TKI stop was the determining prognostic factor for the LMR probability. Interestingly, that the treatment duration did not affect the probability of LMR.Keywords: Chronic myeloid leukemia, treatment-free remission